Phase II drug-metabolizing enzymes (Phase II DMEs)

Phase II drug-metabolizing enzymes represent a diverse group of transferases responsible for the conjugation of xenobiotics and endogenous compounds with polar molecules. These enzymes, which include UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs), N-acetyltransferases (NATs), and glutathione S-transferases (GSTs), generally serve a detoxifying role by increasing the hydrophilicity of substrates to promote their excretion from the body. While typically associated with detoxification, some Phase II reactions can lead to the formation of reactive, toxic, or carcinogenic metabolites. Genetic variations in these enzymes, such as polymorphisms in UGT1A1 or TPMT, are critical determinants of inter-individual variability in drug response and susceptibility to adverse drug reactions. Consequently, they are major considerations in pharmacogenomics and the development of personalized dosing regimens for narrow-therapeutic-index drugs. Note: This entry describes a broad class of enzymes rather than a single molecular target.

Other names

Conjugation enzymesPhase II enzymesDrug-metabolizing enzymesXenobiotic-metabolizing enzymes

Phase II enzymes catalyze the conjugation of endogenous hydrophilic moieties (such as glucuronic acid, sulfate, or glutathione) to functional groups on drugs or Phase I metabolites, typically increasing water solubility to facilitate biliary or renal excretion.